Background: Juvenile Idiopathic Arthritis (JIA) is the most common chronic rheumatologic disease in childhood, characterized by chronic inflammation primarily affecting the joints, which can lead to permanent joint damage. The pathogenesis of JIA involves a dysregulation of innate and adaptive immunity, resulting from an interaction between genetic and environmental factors, whose mechanisms are still not fully understood. Metabolomics is a promising technology for understanding complex diseases such as JIA, allowing for the evaluation of a wide range of endogenous and exogenous metabolites, thus offering new diagnostic and therapeutic perspectives.

Objectives: The aim of this study was to characterize the urinary metabolic profile of children with JIA compared to healthy controls to better understand the pathogenesis of this disease.

Methods: The study involved 58 children aged between 2 and 17 years with JIA (extended oligoarticular, persistent, and polyarticular forms) and 40 healthy controls. Urine samples were collected and analyzed using high-resolution mass spectrometry (HRMS) to identify specific metabolomic profiles through a uniform screening panel including 57 clinically relevant metabolites (NeoBase™ 2 Non-derivatized MSMS kit).

Results: Metabolomic analysis revealed significant differences in urinary metabolites between children with JIA and healthy controls. Specifically, a reduction in glycine levels (p-value = 0.001) and long-chain acylcarnitines (C16.1 p-value = 0.006; C16.1OH.C17 p-value = 0.012; C16OH p-value = 0.029; C20 p-value = 0.017) was observed in patients with JIA compared to healthy controls. Furthermore, through modern machine learning techniques, an increase in creatinuria was observed in children with JIA compared to healthy controls (p-value = 0.099).

Conclusion: The results obtained in this study demonstrated the presence of certain alterations in the urinary excretion of some metabolites. The reduction in long-chain acylcarnitines may indicate increased fatty acid oxidation in these children; however, their specific role in JIA is still unclear. The correlation between increased creatinuria and arthritis suggests that creatine metabolism may be significantly influenced by chronic inflammation and tissue damage associated with the disease. Low levels of urinary glycine in JIA patients are also noteworthy. Some studies suggest that glycine, due to its anti-inflammatory properties, could be used in the treatment of chronic inflammatory diseases such as JIA. However, further studies are needed to fully understand the significance of these findings and their potential clinical and therapeutic applications.

REFERENCES: [1] Dambrova, Maija et al. “Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials.” Pharmacological reviews vol. 74,3 (2022): 506-551. doi:10.1124/pharmrev.121.000408.

[2] Khalatbari-Soltani, Saman, and Hadi Tabibi. “Inflammation and L-carnitine therapy in hemodialysis patients: a review.” Clinical and experimental nephrology vol. 19,3 (2015): 331-5. doi:10.1007/s10157-014-1061-3133.

[3] Szmitko, Paul E et al. “New markers of inflammation and endothelial cell activation: Part I.” Circulation vol. 108,16 (2003): 1917-23. doi:10.1161/01.CIR.0000089190.95415.9F147.

[4] Newgard, Christopher B. “Metabolomics and Metabolic Diseases: Where Do We Stand?.” Cell metabolism vol. 25,1 (2017): 43-56. doi:10.1016/j.cmet.2016.09.018.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.